Avaliação da aterosclerose subclínica em portadores de HDL-colesterol marcadamente elevado

O HDL-c é um fator de risco cardiovascular negativo e sua concentração plasmática apresenta relação inversa com a incidência de eventos cardiovasculares. Entretanto, as evidências relativas ao grupo de indivíduos com níveis de HDL-c acima do percentil 95 da população geral ainda são escassas e o impacto da hiperalfalipoproteinemia (HALP) sobre o risco cardiovascular continua representando motivo de controvérsia na literatura médica. Alguns estudos em populações específicas associam a HALP a aumento do risco cardiovascular. Ao mesmo tempo, outros estudos identificaram populações de indivíduos hipoalfalipoproteinêmicos com marcada longevidade. Assim, demonstrou-se aparente dissociação entre níveis de HDL-c e risco cardiovascular em determinadas populações, reconduzível a aspectos disfuncionais da HDL. O objetivo do presente estudo foi verificar o papel da HALP na determinação do risco cardiovascular; comparar a prevalência de doença cardiovascular subclínica, avaliada por meio da quantificação ultrassonográfica da Espessura Íntimo-Medial Carotídea (EIMC), entre portadores de HDL-c >= 90mg/dL (grupo HALP) e portadores de concentrações de HDL-c atualmente consideradas normais (entre 40 e 50mg/dL para os homens e entre 50 e 60mg/dL para as mulheres); e avaliar características e função da HDL em portadores de HALP por meio do estudo de sua composição, de sua capacidade de efluxo de colesterol, e de sua atividade anti-inflamatória e antioxidante, correlacionando estas características com a presença de doença cardiovascular subclínica avaliada por meio da determinação da EIMC, da Velocidade de Onda de Pulso (VOP) e da presença de Calcificação Arterial Coronariana (CAC) avaliada pela TCMD. Para responder estas perguntas, o presente estudo foi articulado em dois braços: Braço 1: Análise da coorte do estudo ELSA com o objetivo de determinar a prevalência de HALP em uma população geral; definir o perfil demográfico, antropométrico e metabólico dos portadores de HALP; e comparar a prevalência de doença vascular subclínica deste grupo com controles da mesma coorte com níveis normais de HDL-colesterol. Braço 2: Recrutamento de 80 voluntários hígidos e portadores de HALP para avaliação da correlação entre presença de doença vascular subclínica, e aspectos estruturais e funcionais da HDL. Em seus dois braços, o estudo levou a quatro conclusões principais: 1) Níveis marcadamente elevados de HDL-c estão associados a menor espessura íntimo-medial carotídea quando comparados a níveis de HDL-c considerados normais pelas diretrizes vigentes. Embora portadores do fenótipo HALP apresentem, como grupo, um perfil metabólico mais favorável que o encontrado em indivíduos com HDL-c normal, a associação entre EIMC e HALP foi independente dos fatores de risco tradicionais, indicando que a menor prevalência destes últimos em portadores de HDL-c marcadamente elevado justifica apenas parcialmente a menor prevalência de doença vascular subclínica neste grupo; 2) Embora a HALP se apresente como um fenótipo ateroprotetor, há indivíduos com níveis marcadamente elevados de HDL-c que evoluem com doença cardiovascular, clínica ou subclínica. Neste contexto, nossos resultados indicam correlação entre os três métodos avaliados para estudar doença vascular subclínica em portadores de HALP: EIMC, VOP e CAC; 3) Os fatores de risco tradicionais continuam exercendo seu peso na determinação do risco cardiovascular em portadores de HALP. Idade, tabagismo, hipertensão arterial, hipertrigliceridemia e altos níveis de LDL-c apresentaram associação estatisticamente significativa com a presença de doença vascular subclínica no grupo estudado; 4) A avaliação da composição e da função da HDL em portadores de HALP pode permitir identificar indivíduos especificamente mais suscetíveis à aterosclerose. Nossos resultados indicam que, em particular, a atividade anti-inflamatória da HDL, avaliada pela capacidade de inibição da produção de IL-6; o efluxo de colesterol e a capacidade de transferência de triglicérides apresentaram associação independente com menor espessura íntimo-medial carotídea em portadores de HALP, enquanto níveis mais altos de Apo A-IV se associaram a maior grau de doença cardiovascular subclínica

Retrospective study on structural neuroimaging in first-episode psychosis

Background. No consensus between guidelines exists regarding neuroimaging in firstepisode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18–48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age.

General responses of Thoracosphaera heimii grown under a range of pCO2

Ocean acidification is considered a major threat to marine ecosystems and may particularly affect calcifying organisms such as corals, foraminifera and coccolithophores. Here we investigate the impact of elevated pCO2 and lowered pH on growth and calcification in the common calcareous dinoflagellate Thoracosphaera heimii. We observe a substantial reduction in growth rate, calcification and cyst stability of T. heimii under elevated pCO2. Furthermore, transcriptomic analyses reveal CO2 sensitive regulation of many genes, particularly those being associated to inorganic carbon acquisition and calcification. Stable carbon isotope fractionation for organic carbon production increased with increasing pCO2 whereas it decreased for calcification, which suggests interdependence between both processes. We also found a strong effect of pCO2 on the stable oxygen isotopic composition of calcite, in line with earlier observations concerning another T. heimii strain. The observed changes in stable oxygen and carbon isotope composition of T. heimii cysts may provide an ideal tool for reconstructing past seawater carbonate chemistry, and ultimately past pCO2. Although the function of calcification in T. heimii remains unresolved, this trait likely plays an important role in the ecological and evolutionary success of this species. Acting on calcification as well as growth, ocean acidification may therefore impose a great threat for T. heimii.

Investigation of planktic foraminifera from the Norwegian-Greenland Sea

The vertical density gradients in the Nordic Seas are crucial for the preconditioning of the surface water to thermohaline sinking in winter. These gradients can be reconstructed from paired oxygen isotope data in tests of different species of planktonic foraminifera, the isotopic signatures of which represent different calcification depths in the water column. Comparison of d18O values from foraminiferal tests in plankton hauls, sediment traps, and nearby core top samples with the calculated d18Ocalcite profile of the water column revealed species-specific d18O vital effects and the role of bioturbational admixture of subfossil specimens into the surface sediment. On the basis of core top samples obtained along a west-east transect across various hydrographic regions of the Nordic Seas, d18O values of Turborotalita quinqueloba document apparent calcification depths within the pycnocline at 25-75 m water depth. The isotopic signatures of Neogloboquadrina pachyderma (s) reflect water masses near and well below the pycnocline between 70 and 250 m off Norway, where the Atlantic inflow leads to thermal stratification. Here, temperatures in the calcification depth of N. pachyderma (s) differ from sea surface temperature by approximately -2.5°C. In contrast, N. pachyderma (s) calcifies very close to the sea surface (20-50 m) in the Arctic domain of the western Nordic Seas. However, further west N. pachyderma (s) prefers somewhat deeper, more saline water at 70-130 m well below the halocline that confines the low saline East Greenland Current. This implies that the d18O values of N. pachyderma (s) do not fully reflect the freshwater proportion in surface water and that any reconstruction of past meltwater plumes based on d18O is too conservative, because it overestimates sea surface salinity. Minimum d18O differences (<0.2per mil) between N. pachyderma (s) and T. quinqueloba may serve as proxy for sea regions with dominant haline and absent thermal stratification, whereas thermal stratification leads to d18O differences of >0.4 to >1.5per mil.

Planktonic foraminifera of sediment trap samples

Biweekly sediment trap samples and concurrent hydrographic measurements collected between March 2005 and October 2008 from the Cariaco Basin, Venezuela, are used to assess the relationship between [CO3]2- and the area densities (ho A) of two species of planktonic foraminifera (Globigerinoides ruber (pink) and Globigerinoides sacculifer). Calcification temperatures were calculated for each sample using species-appropriate oxygen isotope (d18O) temperature equations that were then compared to monthly temperature profiles taken at the study site in order to determine calcification depth. Ambient [CO3]2- was determined for these calcification depths using alkalinity, pH, temperature, salinity, and nutrient concentration measurements taken during monthly hydrographic cruises. The rho A, which is representative of calcification efficiency, is determined by dividing individual foraminiferal shell weights (±0.43 µg) by their associated silhouette areas and taking the sample average. The results of this study show a strong correlation between rho A and ambient [CO3]2- for both G. ruber and G. sacculifer (R**2 = 0.89 and 0.86, respectively), confirming that [CO3]2- has a pronounced effect on the calcification of these species. Though the rho A for both species reveal a highly significant (p < 0.001) relationship with ambient [CO3]2-, linear regression reveals that the extent to which [CO3]2- influences foraminiferal calcification is species specific. Hierarchical regression analyses indicate that other environmental parameters (temperature and [PO4]3-) do not confound the use of G. ruber and G. sacculifer rho A as a predictor for [CO3]2-. This study suggests that G. ruber and G. sacculifer rho A can be used as reliable proxies for past surface ocean [CO3]2?-

Stable isotope record of planktonic foraminifera of the Atlantic Ocean

The thermal structure of the upper ocean (0-1000 m) is set by surface heat fluxes, shallow wind-driven circulation, and the deeper thermohaline circulation. Its long-term variability can be reconstructed using deep-dwelling planktonic foraminifera that record subsurface conditions. Here we used six species (Neogloboquadrina dutertrei, Globorotalia tumida, Globorotalia inflata, Globorotalia truncatulinoides, Globorotalia hirsuta, and Globorotalia crassaformis) from 66 core tops along a meridional transect spanning the mid-Atlantic (42°N to 25°S) to develop a method for reconstructing past thermocline conditions. We estimated the calcification depths from d18O measurements and the Mg/Ca-temperature relationships for each species. This systematic strategy over this large latitudinal section reveals distinct populations with different Mg/Ca-temperature relationships for G. inflata, G. truncatulinoides, and G. hirsuta in different areas. The calcification depths do not differ among the different populations, except for G. hirsuta, where the northern population calcifies much shallower than the southern population. N. dutertrei and G. tumida show a remarkably constant calcification depth independent of oceanographic conditions. The deepest dweller, G. crassaformis, apparently calcifies in the oxygen-depleted zone, where it may find refuge from predators and abundant aggregated matter to feed on. We found a good match between its calcification depth and the 3.2 ml/l oxygen level. The results of this multispecies, multiproxy study can now be applied down-core to facilitate the reconstruction of open-ocean thermocline changes in the past.

Expression of biomineralization-related ion transport genes in Emiliania huxleyi

Biomineralization in the marine phytoplankton Emiliania huxleyi is a stringently controlled intracellular process. The molecular basis of coccolith production is still relatively unknown although its importance in global biogeochemical cycles and varying sensitivity to increased pCO2 levels has been well documented. This study looks into the role of several candidate Ca2+, H+ and inorganic carbon transport genes in E. huxleyi, using quantitative reverse transcriptase PCR. Differential gene expression analysis was investigated in two isogenic pairs of calcifying and non-calcifying strains of E. huxleyi and cultures grown at various Ca2+ concentrations to alter calcite production. We show that calcification correlated to the consistent upregulation of a putative HCO3- transporter belonging to the solute carrier 4 (SLC4) family, a Ca2+/H+ exchanger belonging to the CAX family of exchangers and a vacuolar H+-ATPase. We also show that the coccolith-associated protein, GPA is downregulated in calcifying cells. The data provide strong evidence that these genes play key roles in E. huxleyi biomineralization. Based on the gene expression data and the current literature a working model for biomineralization-related ion transport in coccolithophores is presented.

Environmental controls on the Emiliania huxleyi calcite mass

Although ocean acidification is expected to impact (bio)calcification by decreasing the seawater carbonate ion concentration, [CO3]2-, there exists evidence of non-uniform response of marine calcifying plankton to low seawater [CO3]2-. This raises questions on the role of environmental factors other than acidification and on the complex physiological responses behind calcification. Here we investigate the synergistic effect of multiple environmental parameters, including temperature, nutrient (nitrate and phosphate) availability, and seawater carbonate chemistry on the coccolith calcite mass of the cosmopolitan coccolithophore Emiliania huxleyi, the most abundant species in the world ocean. We use a suite of surface (late Holocene) sediment samples from the South Atlantic and southwestern Indian Ocean taken from depths lying well above the modern lysocline. The coccolith calcite mass in our results presents a latitudinal distribution pattern that mimics the main oceanographic features, thereby pointing to the potential importance of phosphorus and temperature in determining coccolith mass by affecting primary calcification and possibly driving the E. huxleyi morphotype distribution. This evidence does not necessarily argue against the potentially important role of the rapidly changing seawater carbonate chemistry in the future, when unabated fossil fuel burning will likely perturb ocean chemistry beyond a critical point. Rather our study highlights the importance of evaluating the combined effect of several environmental stressors on calcifying organisms to project their physiological response(s) in a high CO2 world and improve interpretation of paleorecords.

Sea surface temperature (Mg/Ca) from ODP Hole 161-977A

Mg/Ca, Sr/Ca, and stable isotope measurements have been performed on tests from the planktonic foraminifers Globigerinoides ruber (white), Globigerina bulloides, and Neogloboquadrina pachyderma (right coiling) in samples from Ocean Drilling Program site 977A in the Alboran Sea (Western Mediterranean). The evolution of different water masses between 250 and 150 ka is described. Warm substages were characterized by strong seasonality and thermal stratification of the water column. By contrast, less pronounced seasonality and basin stratification seem to prevail during cold substages. Several periods of stratification due to the low salinity of the upper water mass occurred during the formation of organic-rich layers and also during a possible Heinrich-like event at 220 ka. The three foraminifer species studied show a common and large shell Sr/Ca variability in short timescales, suggesting changes in the global ocean Sr/Ca ratio as one of the main causes of variations in shell composition.

Stable carbon and oxygen isotope composition of benthic foraminifera

Seventeen surface sediment samples from the North Atlantic Ocean off NE-Greenland between 76° and 81°N, and nine samples from the South Atlantic Ocean close to Bouvet Island between 48° and 55°S were taken with the aid of a Multiple Corer and investigated for their live (Rose Bengal stained) benthic foraminiferal content within the upper 15 cm of sediment. Preferentially endobenthic Melonis barleeanum, Melonis zaandami, and Bulimina aculeata as well as preferentially epibenthic Lobatula lobatula were counted from 1-cm-thick sediment slices each and analyzed for stable carbon and oxygen isotopic compositions of their calcareous tests. Live and dead specimens were counted and measured separately. The carbon isotopic composition of the foraminifera was compared to that of the dissolved inorganic carbon (DIC) of simultaneously sampled bottom water. During a period of one month, one station off NE-Greenland was replicately sampled once every week and samples were processed as above. Live specimens of Lobatula lobatula are confined to the uppermost two centimeters of sediment. Live specimens of Melonis spp. are found down to 8 cm within the sediment but with a distinct sub-surface maximum between 2 and 5 cm. The down-core distribution of live Bulimina aculeata shows a distinct surface maximum in the top centimeter and constant but low numbers down to 11-cm subbottom depth. The average stable carbon isotopic composition (d13C versus per mil PDB) of live Lobatula lobatula off NE-Greenland is by 0.4±0.1 per mil higher than the d13CDIC of the ambient bottom water at the time of sampling. There is evidence that this species calcify before the ice-free season, when bottom water d13CDIC is supposed to be higher. This would reconfirm the one-to-one relationship between d13C of ambient water DIC and cibicids, widely used by paleoceanographers. Live Melonis barleeanum show a negative offset from bottom water DIC of -1.7±0.6 per mil in the uppermost sediment and of -2.2±0.5 per mil in 3-4-cm subbottom depth. All d13C values of live Melonis spp. decrease within the upper four centimeters, regardless of the time of sampling and site investigated. The offset of live Bulimina aculeata from bottom water d13CDIC values of 8 stations rather constantly amounts to -0.6±0.1 per mil, no matter what subbottom depth the specimens are from. At one station however, where is strong indication of elevated organic carbon flux, the negative offset averaged over all sub-bottom depths increases to -1.5±0.2 per mil. Buliminids actively move within the sediment and by this either record an average isotope signal of the pore water or the signal of one specific calcification depth. The recorded signal, however, depends on the organic carbon flux and reflects general but site-specific pore water d13CDIC values. If compared with epibenthic d13C values from the same site, not influenced by pore water and related phytodetritus layer effects, Buliminad13C values bear some potential as a paleoproductivity proxy. Specimens of Melonis spp. seem to prefer a more static way of life and calcify at different but individually fix depths within the sediment. Although live specimens thus record a stratified pore water d13C signal, there is no means yet to correct for bioturbational and early diagenetic effects in fossil faunas.

Figure 5. Trace metal analysis of sediment core PS1506-1

An increase in whole ocean alkalinity during glacial periods could account, in part, for the drawdown of atmospheric CO2 into the ocean. Such an increase was inevitable due to the near elimination of shelf area for the burial of coral reef alkalinity. We present evidence, based on down-core measurements of benthic foraminiferal B/Ca and Mg/Ca from a core in the Weddell Sea, that the deep ocean carbonate ion concentration, [CO3 2-], was elevated by ~25 µmol/kg during each glacial period of the last 800 kyrs. The heterogeneity of the preservation histories in the different ocean basins reflects control of the carbonate chemistry of the deep glacial ocean in the Atlantic and Pacific by the changing ventilation and chemistry of Weddell Sea waters. These waters are more corrosive than interglacial northern sourced waters, but not as undersaturated as interglacial southern sourced waters. Our inferred increase in whole ocean alkalinity can be reconciled with reconstructions of glacial saturation horizon depth and the carbonate budget, if carbonate burial rates also increased above the saturation horizon as a result of enhanced pelagic calcification. The Weddell records display low [CO3 2-] during deglaciations and peak interglacial warmth, coincident with maxima in %CaCO3 in the Atlantic and Pacific Oceans. Should the burial rate of alkalinity in the more alkaline glacial deepwaters outstrip the rate of alkalinity supply, then pelagic carbonate production by the coccolithophores, at the end of the glacial maximum could drive a decrease in ocean [CO3 2-] and act to trigger the deglacial rise in pCO2.

Absolute abundances of benthic foraminifers and stable isotopes from the Alvin dives 3709-3712

The presence of gas hydrates on the Blake Ridge diapir, northeastern Atlantic Ocean, offers an opportunity to study the impact of methane seepage on the ecology and geochemistry of benthic foraminifera in the late Holocene. Three push cores, covering a time span of ~ 1000 yrs, were retrieved from three distinct microhabitats at the top of the diapir at a water depth of ~ 2150 m: (i) sediments away from seepage (control core), (ii) sediments overlain by clusters of methanotrophic and thiotrophic bivalves, and (iii) chemoautotrophic microbial mats. The foraminiferal assemblages at the two seep sites are marked by a reduction in benthic foraminiferal species diversity, coupled with a near-absence of agglutinated species. However, an opportunistic population rise in CH4- or H2S-tolerant calcareous species (e.g., Globocassidulina subglobosa and Cassidulina laevigata) that utilize the abundant trophic resources at the seeps has led to an increase in the overall assemblage density there. The delta18O and delta13C values of three species of benthic foraminifera - Gyroidinoides laevigatus, Globocassidulina subglobosa, and Uvigerina peregrina - and the planktonic species Globorotalia menardii were acquired from all three cores. The benthic species from methane seeps yield delta13C values of 0.1 to - 4.2 (per mil VPDB), that are distinctly more 13C-depleted relative to the delta13C of 0.4 to - 1.0 (per mil VPDB) at the control (off seep) site. The species from a mussel-bed site exhibit more negative delta13C values than those from microbial mats, possibly reflecting different food sources and higher rate of anaerobic oxidation of methane. The positive delta13C values in the paired planktonic species suggest that authigenic carbonate precipitation did not overprint the observed 13C depletions. Hence the probable cause of negative delta13C of benthic foraminifera is primary calcification from Dissolved Inorganic Carbon (DIC) containing mixed carbon fractions from (a) highly 13C-depleted, microbially-oxidized methane and (b) a seawater source.

Results of a sediment profile and water analyses from Lake Hancza in northeastern Poland

We investigated the sedimentary record of Lake Hancza (northeastern Poland) using a multi-proxy approach, focusing on early to mid-Holocene climatic and environmental changes. AMS 14C dating of terrestrial macrofossils and sedimentation rate estimates from occasional varve thickness measurements were used to establish a chronology. The onset of the Holocene at c. 11600 cal. a BP is marked by the decline of Lateglacial shrub vegetation and a shift from clastic-detrital deposition to an autochthonous sedimentation dominated by biochemical calcite precipitation. Between 10000 and 9000 cal. a BP, a further environmental and climatic improvement is indicated by the spread of deciduous forests, an increase in lake organic matter and a 1.7% rise in the oxygen isotope ratios of both endogenic calcite and ostracod valves. Rising d18O values were probably caused by a combination of hydrological and climatic factors. The persistence of relatively cold and dry climate conditions in northeastern Poland during the first one and a half millennia of the Holocene could be related to a regional eastern European atmospheric circulation pattern. Prevailing anticyclonic circulation linked to a high-pressure cell above the retreating Scandinavian Ice Sheet might have blocked the influence of warm and moist Westerlies and attenuated the early Holocene climatic amelioration in the Lake Hancza region until the final decay of the ice sheet.